PAK-1 Expression in Pancreatic Ductal Adenocarcinoma: A Tissue Microarray Study

Objective: PAK-1, a member of p21-activated serine/threonine protein kinases family, plays an important role in regulating cell motility and invasiveness. To our knowledge, it has not been investigated in pancreatic ductal adenocarcinoma (PDA) yet. Material and Method: Expression level of PAK-1 was tested in a set of tissue microarray containing 98 cases of PDA. Based on the degree of expression level (calculated by an established scoring system incorporating the extent and the intensity of labeling), cases were assigned to one of 4 categories: 0-none, 1-minimal, 2-moderate, and 3-significant. Expression levels were correlated with clinicopathologic features, prognostic parameters, survival, the archival data on K-ras mutation (PCR) and DPC4, p53, p21, p27 and Her2/neu. Results: PAK-1 had a weak expression in ducts and acini while the islets were not stained. In PDAs, 35, 42, and 21 cases had significant, moderate and minimal expression, respectively. The expression had a strong inverse correlation with tumor grade (p=0.04). Cases with significant PAK-1 expression had a much better overall survival (median 24 months) compared to those with moderate and minimal expression (median 7 months) (Chi-square=41.07, p=0.001). Cox Proportional-Hazards Regression Analysis showed that PAK1 expression was independently correlated with better survival (p=0.0001). PAK-1 expression also had a strong correlation with DPC4 expression (p=0.035). No significant association with K-ras, p53, p21, p27 or Her2/neu was found. Conclusion: In contrast to breast and colorectal cancers, PAK-1 expression seems to be a good prognostic factor in PDA. Correlation of PAK-1 and DPC4 expression, suggests that PAK-1 expression may be associated with TGF-beta signaling and has a different role in PDA compared to breast and colorectal cancers. Further studies are needed to explore the role of PAK-1 in PDA.